title: Prostate cancer progression correlates with increased humoral immune response to a human endogenous retrovirus GAG protein.
abstract: OBJECTIVE
  Human endogenous retroviruses (HERV) encode 8% of the human genome. While HERVs may play a role in autoimmune and neoplastic disease, no mechanistic association has yet been established. We studied the expression and immunogenicity of a HERV-K GAG protein encoded on chromosome 22q11.23 in relation to the clinical course of prostate cancer.
  
  
  METHODS
  In vitro expression of GAG-HERV-K was analyzed in panels of normal and malignant tissues, microarrays, and cell lines, and effects of demethylation and androgen stimulation were evaluated. Patient sera were analyzed for seroreactivity to GAG-HERV-K and other self-antigens by ELISA and seromics (protein array profiling).
  
  
  RESULTS
  GAG-HERV-K expression was most frequent in prostate tissues and regulated both by demethylation of the promoter region and by androgen stimulation. Serum screening revealed that antibodies to GAG-HERV-K are found in a subset of patients with prostate cancer (33 of 483, 6.8%) but rarely in male healthy donors (1 of 55, 1.8%). Autoantibodies to GAG-HERV-K occurred more frequently in patients with advanced prostate cancer (29 of 191 in stage III-IV, 21.0%) than in early prostate cancer (4 of 292 in stages I-II, 1.4%). Presence of GAG-HERV-K serum antibody was correlated with worse survival of patients with prostate cancer, with a trend for faster biochemical recurrence in patients with antibodies to GAG-HERV-K.
  
  
  CONCLUSIONS
  Preferential expression of GAG-HERV-K ch22q11.23 in prostate cancer tissue and increased frequency of autoantibodies observed in patients with advanced prostate cancer make this protein one of the first bona fide retroviral cancer antigens in humans, with potential as a biomarker for progression and biochemical recurrence rate of prostate cancer. Clin Cancer Res; 19(22); 6112-25. ©2013 AACR.
authors.affiliation: Authors' Affiliations: Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center; Departments of Surgery, Medicine, Pathology, Biostatistics, and Immunology, Memorial Sloan-Kettering Cancer Center; NYU Langone Medical Center, New York; Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama; RIKEN Bioresource Center, Tsukuba, Ibaraki, Japan; and Klinik für Onkologie und Hämatologie, Krankenhaus Nordwest, Frankfurt, Germany.
authors.forename: Bernardo Sgarbi
authors.initials: BS
authors.lastname: Reis
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Denise
authors.initials: D
authors.lastname: Frosina
authors.forename: Megan
authors.initials: M
authors.lastname: Holz
authors.forename: Erika
authors.initials: E
authors.lastname: Ritter
authors.forename: Eiichi
authors.initials: E
authors.lastname: Nakayama
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ishida
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Obata
authors.forename: Brett
authors.initials: B
authors.lastname: Carver
authors.forename: Howard
authors.initials: H
authors.lastname: Scher
authors.forename: Peter T
authors.initials: PT
authors.lastname: Scardino
authors.forename: Susan
authors.initials: S
authors.lastname: Slovin
authors.forename: Sumit K
authors.initials: SK
authors.lastname: Subudhi
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.forename: Caroline
authors.initials: C
authors.lastname: Savage
authors.forename: James P
authors.initials: JP
authors.lastname: Allison
authors.forename: Jonathan
authors.initials: J
authors.lastname: Melamed
authors.forename: Elke
authors.initials: E
authors.lastname: Jäger
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
mesh_terms: D000368:Aged; D000906:Antibodies / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D002892:Chromosomes, Human, Pair 22 / Q000821:virology; D019175:DNA Methylation; D018450:Disease Progression; D020077:Endogenous Retroviruses / Q000276:immunology*; D015683:Gene Products, gag / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D013534:Survival
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D015683:Gene Products, gag; C465545:HERV-K10gag protein, K10 retrovirus